Abstract

Resistant hypertension (RHTN), defined as an uncontrolled blood pressure despite the use of multiple antihypertensive medications, is an increasing clinical problem associated with increased cardiovascular (CV) risk, including stroke and target organ damage. Genetic variability in blood pressure (BP)-regulating genes and pathways may, in part, account for the variability in BP response to antihypertensive agents, when taken alone or in combination, and may contribute to the RHTN phenotype. Pharmacogenomics focuses on the identification of genetic factors responsible for inter-individual variability in drug response. Expanding pharmacogenomics research to include patients with RHTN taking multiple BP-lowering medications may identify genetic markers associated with RHTN. To date, the available evidence surrounding pharmacogenomics in RHTN is limited and primarily focused on candidate genes. In this review, we summarize the most current data in RHTN pharmacogenomics and offer some recommendations on how to advance the field.

Multiple interrelated pathways involved in the pathogenesis of RHTN. Increased activity of sympathetic nervous system may activate the renal sympathetic efferents with a subsequent activation of RAAS. Excessive aldosterone promotes vascular inflammation and remodeling and may also trigger the activation of sympathetic nervous system. Vascular inflammation derived by excessive aldosterone or activated RAAS may contribute to endothelial dysfunction and arterial stiffness leading to RHTN. The double-headed arrows highlight the interplay of several pathogenic mechanisms in RHTN